1. Field of the Invention
The present invention relates to new cardenolide derivatives, and in particular amino-amides of amino-3-cardenolides as well as their mineral or organic salts, to their preparation and to their therapeutic application.
2. Description of the Prior Art
Numerous natural substances derived from cardiotonic heterosides are used therapeutically for the treatment of cardiac incapacity. For example, it is known that the cardiotonic activity of cardenolide-glycosides such as digitoxin is particularly dependent upon the structure of the cardenolide moiety and on the nature of the sugar-containing chain at 3.beta.. However, these natural substances generally present a low therapeutic margin, which renders their utilization delicate. Hence there is interest in preparing compositions of similar structure but possessing a strong cardiotonic activity associated with low toxicity.
Thus, it was proposed to prepare cardenolide derivatives having an amino group directly attached to the carbon in the 3 position of the steroid ring starting from oxo-3 cardenolides by reaction with hydroxylamine to form the corresponding oxime which is then reduced by catalytic hydrogenolysis. Also known are other compositions obtained by attaching an appropriate substituent at the 3 position of the cardenolide moiety, for example, an amino residue. Such compositions are described in French Pat. Nos. 2,085,722 and 2,191,694.
However, the presence of the amino residue confers basic properties to these compounds.
Also cardenolide derivatives such as the esters and aminoacids of cardenolides, obtained by coupling cardiotonic genins and amino diacids, are known as described in French patent application No. 75.15462 (equivalent to U.S. Pat. No. 4,060,607).